The present invention is directed to a method of using somatostatin or a somatostatin analogue to inhibit the proliferation of Helicobacter pylori (H. pylori), which comprises administering to a patient in need thereof an effective amount of said somatostatin or somatostatin analogue. Preferably, a somatostatin sub-type receptor 2 (SSTR-2) selective somatostatin analogue is administered in a method of this invention.
A growing body of evidence supports a crucial etiological role of H. pylori in the pathogenesis of various gastroduodenal diseases and disorders such as peptic ulcers, gastric cancer, gastric lymphoma, MALT (mucosa-associated lymphoid tissue) lymphoma, gastritis with severe abnormality and after early gastric cancer resection. H. pylori can only survive in the gastric mucous layer covering the gastric epithelial cells (Warren, J. R., Marshall, B. J., Lancet, 1983;1:1273-1275, and Marshall, B. J., Warren, J. R., Lancet, 1984;1:1311-1314). Several bioactive peptides such as gastrin and somatostatin, which exist not only in the gastric mucosa (gastrin-containing G-cells and somatostatin containing D-cells) but also in gastric juice, play an important pathophysiological role in gastroduodenal function (Rao, R. K., Life Sci., 1991;48:1685-1704). It has been demonstrated that levels of somatostatin-like immunoreactivity both in the antral mucosa and in gastric juice are lower in subjects infected with H. pylori compared with H. pylori negative subjects (Kaneko, H., et al., Dig. Dis. Sci. 1992;37:409-416). Others have demonstrated that H. pylori infection decreases mucosal somatostatin content, D-cell number and somatostatin messenger RNA (mRNA) expression and that eradication of H. pylori reverses the somatostatin-related parameters mentioned above (Moss, S. F., et al., Lancet, 1992; 340:930-932; Sumii, M., et al., Am. J. Gastroenterol., 1994;89:1515-1519; Calam. J., Ann. Med. 1995;27:569-573). From these lines of evidence, somatostatin-linked pathogenesis in H. pylori-induced mucosal damage has been proposed. Moreover, somatostatin not only shows gastroprotective property by decreasing acid secretion mediated via inhibiting gastrin secretion, but also regulates the proliferation and differentiation of several lines of cells (Chiba, T., Yamada, T., Gut somatostatin. In: Walsh, J. H., Dockray, G. J., ed., Gut peptides: Biochemistry and Physiology. New York: Raven, 1994:123-145). However, an effect of somatostatin on H. pylori proliferation remains unknown.
As a cure for H. pylori infection in several gastroduodenal diseases, treatment with certain drugs have been used, such as amoxycillin, clarithromycin, metronidazole and tinidazole, but the current pharmaceutical treatments have undesirable side-effects (Lee, J., O'Morain, C., Gastroenterology, 1997;113:S99-S106). Thus, there is a need for a drug which avoids the undesirable side-effects.